Angiopoietin-1 variant, COMP-Ang1 attenuates hydrogen peroxide-induced acute lung injury.
10.3858/emm.2008.40.3.320
- Author:
So Ri KIM
1
;
Kyung Sun LEE
;
Seoung Ju PARK
;
Kyung Hoon MIN
;
Ka Young LEE
;
Yeong Hun CHOE
;
Sang Hyun HONG
;
Gou Young KOH
;
Yong Chul LEE
Author Information
1. Department of Internal Medicine and Airway Remodeling Laboratory, Chonbuk National University Medical School, Jeonju 561-180 Korea. leeyc@chonbuk.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
angiopoietin-1;
capillary permeability;
COMP-Ang1 fusion protein;
hydrogen peroxide;
lung;
pneumonia;
reactive oxygen species;
vascular endothelial growth factor A
- MeSH:
Acute Lung Injury/chemically induced/complications/*drug therapy/metabolism;
Administration, Inhalation;
Airway Resistance/drug effects;
Animals;
Bronchial Hyperreactivity/drug therapy/etiology;
Bronchoalveolar Lavage Fluid;
Capillary Permeability/*drug effects;
Cytokines/antagonists & inhibitors;
Female;
Hydrogen Peroxide/adverse effects;
Hypoxia-Inducible Factor 1, alpha Subunit/antagonists & inhibitors;
Intercellular Adhesion Molecule-1/metabolism;
Mice;
Mice, Inbred BALB C;
NF-kappa B/antagonists & inhibitors;
Pneumonia/*drug therapy/etiology;
Recombinant Fusion Proteins/*administration & dosage;
Vascular Cell Adhesion Molecule-1/metabolism
- From:Experimental & Molecular Medicine
2008;40(3):320-331
- CountryRepublic of Korea
- Language:English
-
Abstract:
Reactive oxygen species (ROS) play a crucial role in acute lung injury. Tissue inflammation, the increased vascular permeability, and plasma exudation are cardinal features of acute lung injury. Angiopoietin-1 (Ang1) has potential therapeutic applications in preventing vascular leakage and also has beneficial effects in several inflammatory disorders. Recently developed COMP-Ang1 is more potent than native Ang1 in phosphorylating tyrosine kinase with immunoglobulin and EGF homology domain 2 receptor in endothelial cells. However, there are no data on effects and related molecular mechanisms of COMP- Ang1 on ROS-induced acute lung injury. We used hydrogen peroxide (H2O2)-inhaled mice to evaluate the effect of COMP-Ang1 on pulmonary inflammation, bronchial hyper-responsiveness, and vascular leakage in acute lung injury. The results have revealed that VEGF expression, the levels of IL-4, TNF-alpha, IL-1 beta, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in lungs, the levels of hypoxia-inducible factor-1alpha (HIF-1 alpha) and NF-kappa B in nuclear protein extracts, phosphorylation of Akt, and vascular permeability were increased after inhalation of H2O2 and that the administration of COMP-Ang1 markedly reduced airway hyper-responsiveness, pulmonary inflammation, plasma extravasation, and the increases of cytokines, adhesion molecules, and VEGF in lungs treated with H2O2. We have also found that the activation of HIF-1a and NF-kappa B and the increase of phosphoinositide 3-kinase activity in lung tissues after H2O2 inhalation were decreased by the administration of COMP-Ang1. These results suggest that COMP-Ang1 ameliorates ROS-induced acute lung injury through attenuating vascular leakage and modulating inflammatory mediators.
